MS-553 reduced BCR and Wnt/β-catenin signaling, overcame stromal cell mediated protection, and synergized with venetoclax in CLL samples. Furthermore, MS-553 delayed disease progression and prolonged survival in the Eµ-MTCP1 murine model of CLL. Collectively our results demonstrate that selective inhibition of PKCβ has the potential to overcome BTKi-resistant CLL.

This work provides the foundation for clinical validation of small-molecule inhibitors synergistic with PTC-596 to improve the durability of remissions and extend survival of patients with treatment-refractory Group 3 MB.

P1, N=45, Recruiting, Shenzhen MingSight Relin Pharmaceuticals Co., Ltd. | Trial completion date: Jul 2025 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Oct 2026

P1/2, N=12, Not yet recruiting, MingSight Pharmaceuticals, Inc | Trial completion date: Dec 2027 --> Dec 2028 | Initiation date: Jul 2025 --> Jul 2026 | Trial primary completion date: Sep 2027 --> Sep 2028

We further propose I-BET-762 and Enzastaurin as potential therapeutic candidates for glioma. In conclusion, the four-gene signature we identified and the corresponding risk score model constructed from it provide valuable tools for the prognosis prediction of glioblastoma multiforme (GBM) and may guide personalized treatment strategies. The least absolute shrinkage and selection operator (LASSO) risk score has demonstrated significant prognostic evaluation utility in clinical GBM patients, bringing potential implications for patient stratification and the optimization of treatment regimens.

P1/2, N=12, Not yet recruiting, MingSight Pharmaceuticals, Inc

P1, N=45, Recruiting, Shenzhen MingSight Relin Pharmaceuticals Co., Ltd. | Suspended --> Recruiting

By taking advantage of a library screening with various kinase inhibitors, we found that the small-molecule inhibitor enzastaurin targeting protein kinase C (PKC) could overcome resistance in TNBC cells. Moreover, the efficiency of dual treatment was largely determined by AURKB, implying that AURKB could be a potential predictive marker for stratifying patients who may benefit from the combinatorial treatment. Collectively, our study not only unravels a novel underlying mechanism for paclitaxel resistance in TNBC but also provides a new potential combinatorial therapeutic strategy in the clinic.

The prototype epoxytigliane, EBC-46 (tigilanol tiglate), is a potent anti-cancer agent in clinical development for local treatment of a range of human and animal tumors...PKC-βI/-βII isoform inhibition by enzastaurin (1 μM), significantly inhibited HaCaT proliferation and wound repopulation responses induced by both epoxytiglianes, especially at 1.51-151 nM. PKC-α inhibitor, Ro 31-8220 mesylate (10 nM), exerted lesser inhibitory effects on HaCaT responses...Phospho-PKC (p-PKC) studies confirmed that epoxytiglianes transiently activated classical PKC isoforms (p-PKCα, p-PKC-βI/-βII, p-PKCγ) in a dose- and time-dependent manner. By identifying how epoxytiglianes stimulate classical PKCs to facilitate keratinocyte healing responses and re-epithelialization, these findings support further epoxytigliane development as topical therapeutics for clinical situations involving impaired re-epithelialization, such as non-healing wounds in skin.

P2, N=138, Recruiting, DermBiont, Inc. | Trial completion date: Jul 2025 --> Oct 2025 | Trial primary completion date: Jan 2025 --> Apr 2025

P1/2, N=8, Terminated, MingSight Pharmaceuticals, Inc | N=38 --> 8 | Trial completion date: Jul 2026 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Apr 2026 --> Nov 2023; The study is terminated due to major protocol revisions.

P1, N=45, Suspended, Shenzhen MingSight Relin Pharmaceuticals Co., Ltd. | Trial completion date: Jan 2024 --> Jul 2025 | Recruiting --> Suspended | Trial primary completion date: Dec 2023 --> Jun 2025